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We examined the hypothesis that both misoprostol (miso), a prostaglandin E(1) (PGE(1)) analog, and nonsteroidal anti-inflammatory drugs (NSAIDs) have significant and largely inhibitory effects on T-cell activation and, consequently, influence T-cell function. Studies were done using a macrophage-independent system for T-cell activation by mitogenic combinations of immobilized anti-T-cell monoclonal antibodies (mabs), including combinations of anti-CD3 with anti-CD4 or anti-CD6. The results indicate that misoprostol, like other prostaglandins, can inhibit T-cell proliferation and the expression of mRNAs for cytokines critical in T-cell growth and immunoregulation. Somewhat higher concentrations of misoprostol are required than of PGE(1) to achieve comparable effects. However, even very low doses of misoprostol (0.01mgr;g ml(minus sign1)) may sometimes enhance T-cell activation. The effects on cytokine mRNA are not uniform; for a given dose and agent, one cytokine mRNA may be enhanced while another is unchanged or diminished. Whether a response is increased or decreased depends on several factors, including the dose of misoprostol or other PG tested, the strength of the response on which the agent is acting, and the level of preexisting activation or cytokine gene expression. Similar findings can be seen with treatment in vitro with NSAIDs, including sodium salicylate. When PGs (including misoprostol) and NSAIDs are combined, effects are often additive and sometimes appear synergistic, but paradoxical results can also occur, whereby each agent separately may be modestly inhibitory, but together they are stimulatory. The in vitro response of T cells to both PGs and NSAIDs (either separately or together) is, thus, highly complex. These data support the notion that these agents may have significant effects on the regulation of T-cell activation and function.

Background Familial aggregation of dementia with Lewy bodies (DLB) remains unclear. Objectives To determine the degree of family aggregation of DLB by comparing DLB risk between siblings of probands with clinically diagnosed DLB and siblings of probands with clinically diagnosed Alzheimer disease in a cohort of Caribbean Hispanic families and to explore the degree of aggregation of specific clinical manifestations (ie, cognitive fluctuations, visual hallucinations, and parkinsonism) in DLB. Design Familial cohort study. Setting Academic research. Patients We separately compared risks of possible DLB, probable DLB, and clinical core features of DLB (cognitive fluctuations, visual hallucinations, and parkinsonism) between siblings of probands with clinically diagnosed DLB (n = 344) and siblings of probands with clinically diagnosed Alzheimer disease (n = 280) in 214 Caribbean Hispanic families with extended neurologic and neuropsychological assessment. Main Outcome Measures We applied general estimating equations to adjust for clustering within families. In these models, age and proband disease status were independent variables, and disease status of siblings was the measure of disease risk and the dependent variable. Results Compared with siblings of probands having clinically diagnosed Alzheimer disease, siblings of probands having clinically diagnosed DLB had higher risks of probable DLB (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.04-5.04) and visual hallucinations (2.32; 1.16-4.64). They also had increased risks of possible DLB (OR, 1.51; 95% CI, 0.97-2.34) and cognitive fluctuations (1.55; 0.95-2.53). Conclusions Dementia with Lewy bodies and core features of DLB aggregate in families. Compared with siblings of probands having clinically diagnosed AD, siblings of probands having clinically diagnosed DLB are at increased risks of DLB and visual hallucinations. These findings are an important step in elucidating the genetic risk factors underlying DLB and in delineating DLB from other neurodegenerative diseases, such as Alzheimer disease.

Background Familial aggregation of dementia with Lewy bodies (DLB) remains unclear. Objectives To determine the degree of family aggregation of DLB by comparing DLB risk between siblings of probands with clinically diagnosed DLB and siblings of probands with clinically diagnosed Alzheimer disease in a cohort of Caribbean Hispanic families and to explore the degree of aggregation of specific clinical manifestations (ie, cognitive fluctuations, visual hallucinations, and parkinsonism) in DLB. Design Familial cohort study. Setting Academic research. Patients We separately compared risks of possible DLB, probable DLB, and clinical core features of DLB (cognitive fluctuations, visual hallucinations, and parkinsonism) between siblings of probands with clinically diagnosed DLB (n = 344) and siblings of probands with clinically diagnosed Alzheimer disease (n = 280) in 214 Caribbean Hispanic families with extended neurologic and neuropsychological assessment. Main Outcome Measures We applied general estimating equations to adjust for clustering within families. In these models, age and proband disease status were independent variables, and disease status of siblings was the measure of disease risk and the dependent variable. Results Compared with siblings of probands having clinically diagnosed Alzheimer disease, siblings of probands having clinically diagnosed DLB had higher risks of probable DLB (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.04-5.04) and visual hallucinations (2.32; 1.16-4.64). They also had increased risks of possible DLB (OR, 1.51; 95% CI, 0.97-2.34) and cognitive fluctuations (1.55; 0.95-2.53). Conclusions Dementia with Lewy bodies and core features of DLB aggregate in families. Compared with siblings of probands having clinically diagnosed AD, siblings of probands having clinically diagnosed DLB are at increased risks of DLB and visual hallucinations. These findings are an important step in elucidating the genetic risk factors underlying DLB and in delineating DLB from other neurodegenerative diseases, such as Alzheimer disease.

Background The clinical delineation of dementia with Lewy bodies (DLB) from Alzheimer disease (AD) remains unclear. Objectives To compare neuropsychological profiles in DLB and AD among Caribbean Hispanic family members and participants in a population-based epidemiologic sample using extended neuropsychological test batteries and to explore whether these differences were related to heritable factors. Design Cross-sectional study. Setting Clinics in northern Manhattan (New York City), the Dominican Republic, and Puerto Rico. Patients We compared measures of memory, orientation, language, and executive and visuospatial functioning between patients with DLB vs AD in 2 Caribbean Hispanic cohorts, including a family sample (89 patients with DLB and 118 patients with AD) and an epidemiologic sample (70 patients with DLB and 157 patients with AD). Patients with DLB in the family sample were further categorized as patients having at least 2 family members with DLB or as patients having 1 family member with DLB. Main Outcome Measures To determine whether observed differences in cognitive profiles were driven by heritable factors, we repeated analyses in the epidemiologic sample after excluding familial cases. We applied general linear models adjusted for age, sex, educational level, disease duration, and apolipoprotein E e4 (OMIM104310) genotype. Results Patients with DLB in both samples were more severely impaired in orientation, visuoconstruction, and nonverbal reasoning after controlling for potential confounders. Patients having at least 2 family members with DLB had the most severe impairment in memory, followed by patients having 1 family member with DLB, and then by patients with AD. After excluding familial AD and DLB cases in the epidemiologic sample, the differences between the groups persisted but were attenuated. Conclusions Compared with patients having AD, patients having DLB are more severely impaired in various cognitive domains, particularly orientation and visuospatial functioning. The difference seems stronger in familial DLB than in sporadic DLB. Whether this divergence in cognitive functions is caused by gene-gene or gene-environmental interactions remains unclear.

ARDS developed in association with tumor lysis syndrome (TLS) in a patient with non-Hodgkin's lymphoma. Although a number of life-threatening complications have been noted to occur following TLS, this appears to be the first report of ARDS developing in association with TLS.